Yamuna Krishnan’s goal: Find drugs for neurodegenerative diseases

When Yamuna Krishnan finished her postdoctoral training in the UK, she headed home to India, certain that her career would focus on fundamental science and never on entrepreneurship.

Now a chemistry professor at the University of Chicago and the chief science officer of the start-up Esya Labs, she’s learned to never say never.

While working at the National Center for Biological Sciences in Bangalore, India, after her postdoc, Krishnan realized that the DNA-based fluorescence sensors she was designing could potentially be used to diagnose diseases. So she took the leap and moved to the University of Chicago, where she knew she could make connections to bring the sensors to patients.

Her group there has since developed DNA-based sensors to measure pH and chloride ions. The scientists use DNA as a “coat hanger” onto which they can add groups such as ion sensors and recognition elements to get the nanodevices inside cells.

These sensors can detect specific chemical signatures, like ion levels, inside the organelles of cells, especially lysosomes. The concentrations of ions are frequently off balance inside lysosomes in a number of diseases, including neurodegenerative diseases like Alzheimer’s. But there hasn’t been an easy way to measure them.

Seeing the promise of the nanodevices for diagnosing lysosomal storage diseases, graduate student Kasturi Chakraborty urged Krishnan to enter a business plan competition run by the University of Chicago’s Polsky Center for Entrepreneurship and Innovation. “We put together a very compelling science case, but our business case was not great at all,” Krishnan says, recalling their naivete about raising funds. “We didn’t win that competition for the simple reason that our business case was like the case of a 3-year-old.”

But while she was preparing for the competition, Krishnan visited Dhivya Venkat, a friend and serial entrepreneur working in finance in London. Krishnan practiced her pitch on Venkat, who said it needed a lot of work. After dinner and a bottle of wine, Venkat surprised Krishnan by saying she’d come aboard as CEO to make the start-up a reality.

“Everything changed,” Krishnan says. “From then, I understood what it is to have a professional businessperson manage very powerful technology.”

They founded Esya Labs in 2018, with Krishnan in Chicago and Venkat in London. They’ve raised initial funds from friends and family and are now looking for space to set up shop in the Boston area. They plan to open their next funding round this spring.

Esya has three areas of focus. The company is using its lysosomal ion-concentration technology to analyze tissue from clinical trial participants to determine whether patients respond to a drug and to divide the patient population into disease subtypes. It is also helping pharmaceutical firms screen for small molecules that target disease-related ion channels and transporter proteins in cells. And third, the company is working with a partner in India on diagnostics for rapid detection of bacteria and antibiotic resistance.

The experience of starting a company has been both frustrating and exciting, Krishnan says. But she thinks it’s positively affecting her day job as a professor, a position she has no plans to give up. She’s learned to frame her research in terms of the problems she’s trying to solve, not just in terms of cool technology.

Shankar Balasubramanian, Krishnan’s postdoc adviser at the University of Cambridge who has commercialized multiple DNA-related technologies, has followed her career since she left his lab. “It comes as no surprise that she is now launching a biotech company to develop and exploit her excellent scientific discoveries,” he says. “Some of the best biotech companies have been created by scientists with vision, originality, and considerable creative energy, and Yamuna is someone I would place in that class.”

And Krishnan may have caught the entrepreneurial bug. She already has an idea for another company, although she’s not ready to share details.

So much for never working in business.